The embodiments described herein relate generally to label-free detection of renal cancer and, more particularly, to a method and a system for detecting the presence of predetermined proteins via surface enhanced Raman scattering (SERS) or localized surface plasmon resonance. In one embodiment, the predetermined proteins are indicative of renal cancer (e.g., kidney cancer) and a patient's urine is tested for the presence of the predetermined proteins.
Renal cancer (e.g., kidney cancer) is generally silent, frequently fatal, and accounts for 3% of adult malignancies. In the United States in 2009, more than 57,000 cases of kidney cancer were diagnosed, and almost 13,000 deaths occurred that were attributable to this disease. Altogether, this disease represents the sixth leading cause of death due to cancer. According to the SEER Stat Facts of the Kidney Cancer Homepage of the National Cancer Institute, one in 70 adults in the United States will develop kidney cancer during their lifetime. For men, renal cancer is seventh among newly diagnosed cancers in 2009, ahead of both leukemia and pancreatic cancer. For women it is eighth in newly diagnosed cancers, ahead of both ovarian and pancreatic cancer. Renal cancer, when symptomatically diagnosed by the classic triad of flank pain, hematuria and a palpable flank mass, has already metastasized to lymph nodes or other organs in 30-40% of patients. Renal cancer is resistant to chemotherapy, and metastatic disease portends a miserable prognosis.
There are substantial benefits to early detection. If, at diagnosis, the tumor is confined within the renal capsule, survival rates can exceed 70%. Additional benefits of early detection include the opportunities for laparoscopic, as opposed to open, nephrectomy and partial, as opposed to total, nephrectomy. Minimally invasive laparoscopic surgery rather than open laparotomy enables shorter hospitalization, faster recovery, less pain and disability, fewer complications and lower cost. Nephron-sparing partial nephrectomy rather than total nephrectomy preserves renal mass and long-term renal function. Partial nephrectomy is associated with better long-term survival of patients with stage T1b tumors than patients who undergo radical nephrectomy, suggesting that conventional open radical nephrectomy may be considered over-treatment. The desire to preserve renal function and to minimize future chronic kidney disease are compelling factors for early diagnosis of renal cancer. Identifying suitable biomarkers of kidney cancer and development of efficient technology to rapidly and noninvasively detect these biomarkers are important to disease diagnosis and documenting response to therapy.
Kidney cancer causing carcinogens such as trichloroethylene (TCE) are ubiquitously used in industrial and military applications as a degreaser. TCE is a highly toxic industrial solvent and a common contaminant in soil and groundwater at over 1200 sites across the United States, including hundreds of military bases—most prominently Camp Lejeune, N.C., the largest TCE contamination site in the country. Smoking and obesity, also common in military communities, are also risk factors for kidney cancer. Therefore kidney cancer, itself common in the civilian population, is an even greater threat to the health of the military communities, which constitute an at-risk population numbering in the millions. Kidney cancer is a deadly stealth killer, growing silently and undetected, until so large, advanced, and usually metastatic, that symptoms occur. Such cancers are fatal in 95% of the victims. In contrast, if detected early, kidney cancer can be cured in over 70% of the patients. Early detection also enables noninvasive surgery, quick recovery, preserving kidney function, reduction in total cost of care and minimizing disability and loss of worker productivity. There is presently no means to screen at-risk military or associated populations (indeed any population) for kidney cancer.
SERS involves dramatic enhancement (up to 1012 times or more) of the intensity of the Raman scattering from the analyte adsorbed on or in proximity to a metal surface with nanoscale roughness due primarily to the enhanced electromagentic field. Electromagnetic enhancement depends on numerous factors such as distance of the analyte from the metal nanostructure, distance between the nanostructures in the case of dimers and aggregates, size and shape of the nanostructures, composition of the metal, and the excitation wavelength with respect to the plasmon resonance of the metal nanostructures. SERS is a powerful platform for label and label-free biosensing of a wide variety of biomolecules. There are numerous advantages to SERS based biosensors over conventional bioassays such as ELISA, Western blotting and immuno precipitation. The molecule-specific Raman bands (forming a molecular fingerprint) combined with the molecular recognition capability of the capture antibodies immobilized on the metal nanostructure surface enables the label-free detection of the target biomolecules, as described herein. Furthermore, the inherently narrow Raman bands (as opposed to broad fluorescence bands of the other techniques) enable multiplexed detection of multiple analytes in a complex mixture. Prior art SERS systems have poor sensitivity due to the poor light-metal nanostructure interaction. In addition, one often overlooked consideration in the design of SERS substrates for trace detection is the efficiency of sample collection. Known designs based on rigid substrates such as silicon, alumina, and glass resist conformal contact with the surface under investigation, making the sample collection inefficient. Accordingly, SERS substrate designs which enable efficient guiding of the incident and scattered photons complemented with easy access to analytes and their selective binding to enable reliable real-world biological sensors are desirable.